Studies will continue to focus on the molecular aspects of drug interactions as described in the reports of the individual projects. Project I will be concerned with the potential interaction between rifampin and warfarin, rifampin and phenprocoumon, and cimetidine and warfarin in normal human subjects. Project 3 will study the metabolic fate of valproyl CoA and valproyl carnitine, the effect of valproate and delta4-valproate on fatty acid metabolism, the formation of unsaturated metabolites of valproate in general, the mechanism of inhibition of carbamazepine-10,11-epoxide and the inhibitory effect of valproate on the formation of p-hydroxyphenobarbital. Project 4 will examine the hepatoprotective effect of ethanol infused in rats and determine the value of KI in "in vitro" studies. Work on the adriamycin-acetaminophen interaction will begin.